Laboratory of Pharmaceutical Chemistry, Universidade Federal da Paraíba, João Pessoa 58051-085, Brazil.
Department of Molecular Biology and Genetics, Erzurum Technical University, Erzurum 25240, Turkey.
Molecules. 2018 Jun 8;23(6):1382. doi: 10.3390/molecules23061382.
Piplartine () is an alkamide extracted from plants of the genus which shows several pharmacological properties, including antitumor activity. To improve this activity, a series of analogues based on have been synthesized by esterification and amidation using the 3,4,5-trimethoxycinnamic acid-like starting material. During the study, the moieties 3-(3,4,5-trimethoxyphenyl)acrylate and 3-(3,4,5-trimethoxyphenyl)acrylamide were maintained on esters and amides respectively. Meanwhile, functional changes were exploited, and it was revealed that the presence of two aromatic rings in the side-chain was important to improve the cytotoxic activity against the U87MG cell line, such as the compound ()-benzhydryl 3-(3,4,5-trimethoxyphenyl)acrylate (), an ester that exhibited strong cytotoxicity and a similar level of potency to that of paclitaxel, a positive control. Compound had a marked concentration-dependent inhibitory effect on the viability of the U87MG cell line with apoptotic and oxidative processes, showing good potential for altering main molecular pathways to prevent tumor development. Moreover, it has strong bioavailability with non-genotoxic and non-cytotoxic properties on human blood cells. In conclusion, the findings of the present study demonstrated that compound is a promising agent that may find applications combatting diseases associated with oxidative stress and as a prototype for the development of novel drugs used in the treatment of glioblastoma.
白皮杉醇（）是一种从白皮杉属植物中提取的烷酰胺，具有多种药理活性，包括抗肿瘤活性。为了提高这种活性，我们使用 3,4,5-三甲氧基肉桂酸类似物作为起始原料，通过酯化和酰胺化合成了一系列基于 的类似物。在研究过程中，分别将 3-(3,4,5-三甲氧基苯基)丙烯酸酯和 3-(3,4,5-三甲氧基苯基)丙烯酰胺这两个部分保持在酯和酰胺上。同时，我们利用功能变化，发现侧链中存在两个芳环对于提高对 U87MG 细胞系的细胞毒性活性很重要，例如化合物 ()-苯甲基 3-(3,4,5-三甲氧基苯基)丙烯酸酯（），这是一种酯，具有很强的细胞毒性，与阳性对照紫杉醇的效力相似。化合物 对 U87MG 细胞系的活力具有明显的浓度依赖性抑制作用，并伴有凋亡和氧化过程，显示出改变主要分子途径以预防肿瘤发展的良好潜力。此外，它具有很强的生物利用度，对人血红细胞没有遗传毒性和细胞毒性。总之，本研究的结果表明，化合物 是一种很有前途的药物，可能在治疗与氧化应激相关的疾病和作为治疗神经胶质瘤的新型药物的原型方面具有应用潜力。
